Human pluripotent stem cells are expected to revolutionize the accessibility to a variety of human cell types since they have the capacity, under appropriate conditions, to self-renew as well as the ability to form any type of specialized cells of the three germ layers (endoderm, mesoderm, and ectoderm). Of major interest is the endodermal layer since it gives rise to the intestine, pancreas, liver and lung, i.e. organs of the human body failure or damage of which are associated with a great number of disease states and clinical disorders seen today. A great promise thus lies in the in vitro development of organ specific tissue for replacement therapy.
Due to its unique capability among the three germ layers to develop into the above mentioned organs, the endoderm, more specifically the definitive endoderm, plays a central role in the production of organ specific tissue. Thus, there is a constant need to improve the characteristics of in vitro derived endodermal cells which eventually has an impact on the quality and quantity of the organ specific cells and tissue. However, early endoderm development is not well understood, with only a few factors so far identified to drive the differentiation of human pluripotent stem cells towards endoderm. Accordingly, finding further, yet unidentified, factors having an influence on endodermal development is important and will help to optimize the cultivation condition for in vitro production of cells and tissue of endodermal organs.
The importance of DNA methylation during normal embryogenesis and development has long been suspected and the application of DNA demethylating agents can cause reactivation of large swathes of genes in a genome. Previous work has shown that DNA demethylation can be used to direct differentiation of hES cells towards cardiac fate (Yoon et al 2006), presumably by activating genes required for cardiomyogenesis which would normally be methylated and silenced.